MRSA Decolonization in Complicated Carriage (CLEANEST)

MRSA Decolonization in Complicated Carriage - Cluster Randomized Trial

Multicenter open-label cluster randomized controlled trial determining the superiority of doxycycline-rifampicin compared to trimethoprim-rifampicin for the decolonization treatment of complicated MRSA carriership.

Study Overview

• Status: Recruiting
• Conditions: MRSA
• Intervention / Treatment: Drug: doxycycline 200 mg q.d. - rifampicin 600mg b.i.d.; Drug: trimethoprim 200mg b.i.d. - rifampicin 600mg b.i.d.

Detailed Description

Rationale: MRSA decolonization has proven to prevent infection and reduce transmission. It has yet remained undecided which combination of anti-staphylococcal agents is most effective in the treatment of complicated MRSA carriage. A recent cohort study showed the highest success rate of decolonization in patients treated with doxycycline-rifampicin (86%) compared to the other antibiotic combinations (average 69%). However, because of the retrospective study design the validity of the results is limited. A randomized clinical study is necessary to determine if doxycycline-rifampicin is superior to other conventional treatment regimens. The Dutch guideline recommends both doxycycline-rifampicin and trimethoprim-rifampicin as first choice treatments for decolonization of complicated MRSA carriage. Therefore trimethoprim-rifampicin will be the comparator of this study.

Objective: To determine the superiority of doxycycline-rifampicin compared to trimethoprim-rifampicin for the decolonization treatment of complicated MRSA carriership.

Study design: Multicenter open-label cluster randomized controlled trial.

Study population: Adult (>18 years) patients with complicated MRSA carriership, treated at one of the participating outpatient clinics. Sample size 211 patients.

Intervention: Group A: doxycycline 200 mg q.d. - rifampicin 600mg b.i.d. versus Group B: trimethoprim 200mg b.i.d. - rifampicin 600mg b.i.d. All orally, total duration 7 days.

Main study parameters/endpoints: The main study endpoint is the success rate of MRSA decolonization. Successful decolonization is defined as 3 consecutive negative cultures after treatment, with a minimum interval of 7 days.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: MRSA decolonization treatment is already standard clinical practice in the Netherlands. There is no additional burden or risk associated with participation in the study. Both antibiotic regimens (in Group A and Group B) used in the study, are recommended as first-line therapy by the Dutch guideline for the treatment of MRSA carriage. The study is open label, so there is no additional risk of blinding. The number of outpatient visits and follow-up cultures are not different from daily clinical practice in the Netherlands. No invasive procedures will be performed for the purpose of this study.

• Study Type: Interventional
• Enrollment (Estimated): 211
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Annette Westgeest, MD; Phone Number: +3171 5262613; Email: a.c.westgeest@lumc.nl

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • LUMC
    • Contact: Merel Lambregts

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Complicated MRSA carriership. Complicated carriership is defined as having one of the following features: (i) the presence of MRSA located at another site than the nose, (ii) an active infection with MRSA, (iii) in vitro resistance for mupirocin, (iv) active skin lesions, (v) foreign material that connects an internal body site with the outside (e.g., urine catheter, external fixation material), (vi) previously failure of decolonization treatment.

In case of none of the previously mentioned features, this is considered uncomplicated carriership.

- The ability to provide informed consent for the use of their data.

Exclusion Criteria:

• - Presence of any iv-access, urinary catheters or drains (because of high risk of treatment failure)
• Failure of previous decolonization attempt of complicated MRSA carriage
• Allergy or other contra-indication to either doxycycline, rifampicin or trimethoprim (these patients will participate in the observational arm)
• Previous participation in this study (every patient can only participate once)
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; doxycycline 200 mg q.d. - rifampicin 600mg b.i.d.	Drug: doxycycline 200 mg q.d. - rifampicin 600mg b.i.d.; Both first choice treatments in Dutch guideline for MRSA decolonization
Active Comparator: B; trimethoprim 200mg b.i.d. - rifampicin 600mg b.i.d.	Drug: trimethoprim 200mg b.i.d. - rifampicin 600mg b.i.d.; Both first choice treatments in Dutch guideline for MRSA decolonization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
success rate	success rate of MRSA decolonization	3 consecutive negative cultures after treatment, with a minimum interval of 7 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
long term success rate	success rate of decolonization treatment after 1 year	1 year

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Merel Lambregts, MD PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Antiprotozoal Agents; Antiparasitic Agents; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antimalarials; Folic Acid Antagonists; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Cytochrome P-450 CYP2C8 Inhibitors; Doxycycline; Rifampin; Trimethoprim
• Other Study ID Numbers: NL79720.058.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No